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Heart Rejection

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Rejection can occur when the body recognizes the heart as “not part of me; an invader” and tries to get rid of it.  The body “rejects” the heart.  Rejection can occur at any time after transplantation, but is most common in the first several weeks.  Monitoring for rejection will actually require lifelong follow-up. But while your child is in the ICU, this will include a physical exam and EKG daily, as well as frequent blood testing and chest x-rays, and at least one echocardiogram.  Your child may also have a cardiac catheterization with myocardial biopsy to look for rejection before he/she is discharged from the hospital.  During this test, a catheter with a tiny device on its tip is inserted through a vein in the groin or the neck and several small pieces of the heart muscle are taken out to look at under a microscope.  Rejection is treated with very high doses of immune suppression medication for a short time.

Acute Rejection

Acute rejection is an inflammatory reaction involving the heart muscle.  Symptoms of a mild rejection episode are often vague or absent.  They may include lethargy, water retention, weight gain, and fever.  These symptoms, however, are also present during infections and as side effects of medications, which often make a diagnosis more difficult.  Moderate or severe acute rejection generally causes more symptoms.  Irregular heartbeats, changes in blood pressure, dizziness, and shortness of breath commonly occur.  Please notify the Transplant Office if your child experiences any of these symptoms so that proper diagnosis can be made and treatment started promptly.

As the symptoms of early acute rejection are often vague and not always present, routine screening is performed.  EKGs, chest x-rays, blood tests, and heart biopsies and/or echocardiograms are done frequently immediately after transplant and decrease in frequency with time.  Of these tests, the heart biopsy or echocardiogram is the only accurate way to check for rejection (see “Heart Biopsy”).  Sometimes an EKG or chest x-ray may suggest rejection, but a heart biopsy or echocardiogram is the only definitive way to check for rejection at this time.

Although acute rejection can happen anytime after transplant, it most commonly occurs in the first three to six months.  During this time, doses of immunosuppressive medications are deliberately high.  As the body adjusts to the new heart, the doses will decrease.  One year post-transplant the transplant patient will be taking stable doses of these medications.  Acute rejection after this time is uncommon but it can happen and does happen at any time after transplant.

To reduce the risk of acute rejection, all medications must be taken as prescribed.  If medication is not taken after transplant, whether it is one week or ten years later, the body WILL reject the heart.

If moderate or severe acute rejection occurs, your child will be admitted to the hospital. Treatment is with intravenous (IV) steroids (Prednisone).  Biopsies/echocardiograms are performed frequently until the rejection resolves.  Should the steroids not treat the rejection effectively; other more powerful medications can be given. Rejection is very serious and MUST be treated as soon as possible.

Chronic vascular rejection

Chronic vascular rejection is different from the acute form in that it involves the coronary arteries (blood vessels of the heart).  You may hear chronic rejection referred to as “accelerated graft atherosclerosis.”  A simple explanation is that the coronary arteries narrow with a buildup of cholesterol, platelets, and blood clots.  The narrowed arteries allow less oxygen to be supplied to the heart, increasing the chances of a heart attack.  Symptoms may include swelling and shortness of breath with activity, and a gradual decline in exercise tolerance may be noticed.

Unfortunately, the transplant patient will not experience the most common symptom of heart attack - angina or pain.  The lack of pain makes it necessary to routinely check for the presence of chronic vascular rejection.

Chronic vascular rejection can be detected through the use of an angiogram.  Chronic vascular rejection does not generally appear before six months post-transplant and is more common after two to three years.

To reduce the risk of chronic vascular rejection, it is important to follow a low fat, low cholesterol diet.  Following this diet may decrease the level of cholesterol and triglycerides in the bloodstream, reducing the amount available to be deposited in the coronary arteries.  Persantine or aspirin, both mild blood thinners, are also prescribed to allow blood to flow smoothly through the coronary arteries.

Heart Biopsy

A heart biopsy will initially be done every two weeks for the first twelve weeks, monthly for the following three months at nine months and one year post transplant to check for rejection. The procedure is done as an outpatient and takes about an hour.

Your child will be taken to the cardiac catheterization lab and given general anesthesia.  A catheter, or tube, is threaded through a large vein in the neck or groin into the right ventricular chamber of the heart.  Through this tube, a wire with a pincher on the end is threaded into the heart where it extracts six to eight pieces of heart muscle, each no bigger than a pin point. The removal of these pieces will not damage the heart.  Occasionally, the heart will display some irregular beats during this procedure but this typically goes away after the heart muscle is no longer irritated by the pincher.  After the specimens are obtained, the catheter is removed, pressure is held over the site for 20 minutes to control any potential bleeding and a band-aid is applied to the insertion site.  The biopsy specimens are sent to a pathologist who examines them under a microscope and determines if the transplanted heart is in rejection.

The heart or endomyocardial biopsy (EMB) is recognized as the most effective measure for diagnosing rejection in the heart transplant patient as well as the post-treatment management of rejection.

The development of the technique for EMB to monitor rejection contributed to the current success of cardiac transplantation.  The evaluation of rejection by EMB is essential for clinical management.  EMB’s are performed routinely at frequent intervals during the early post-operative period, when acute rejection is most often seen, and then at less frequent but regular intervals thereafter.

Heart Biopsy Grading Scale

Grade O (No Acute Rejection)

Grade 0 is used when there is no evidence of acute rejection or cell damage on the biopsy specimens.  No change in medications is necessary.

Grade 1R (Focal, Mild Acute Rejection)

Grade 1R represents a greater immune system response with no cell damage.  One or more pieces of the biopsy tissue may be involved. No change in medications is necessary.

Grade 2R (Moderate Acute Rejection)

Grade 2 an even greater immune system response with possible cell damage.  One or more pieces of biopsy tissue may be involved.  At least a three day hospitalization and IV steroids will be used to treat this rejection.

Grade 3R (Diffuse, Borderline Severe Acute Rejection)

Grade 3R represents a greater immune system response and an inflammatory process within several pieces of biopsy tissue.  Cell damage is present.  Swelling, hemorrhage, and vasculitis can also be present.  Again, hospitalization with IV steroid administration will be used.  Other anti-rejection agents are used if the rejection is resistant to the steroids.

If moderate or severe rejection is diagnosed, it is treated with intravenous steroid therapy, using Solumedrol, and then using oral steroids to efficiently reduce the dosage.

Once a grade 2 or 3 rejection is discovered, your child will need to have another biopsy in 2 weeks in order for us to determine the rejection has gone.  Most children are put on an oral prednisone taper that will end shortly before their next biopsy.
 

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